Versatile yet biocompatible bio-materials are in high demand in nearly every industry, with biological and biomedical engineering relying heavily on common biomaterials like alginate polymers. Alginate is a very common substance found in various marine plants which can easily be extracted and purified through cheap nonhazardous methods. A key characteristic of alginate polymers includes easily manipulatable physical properties due to its inert but functional chemical composition. Factors including its functional versatility, long-term polymer stability and biocompatibility have caused alginate-based technologies to draw major attention from both the scientific and industrial communities alike. While also used in food industry manufacturing and standard dental procedures, this chapter will focus on a discussion of the both clinical and nonclinical use of alginate-based technologies in transplantation for regenerative cell and drug delivery systems. In addition, we overview the immune system response prompted following implantation of alginate hydrogels. Consequences of immune cell reactivity to foreign materials, such as inflammation and the foreign body response (FBR), are also analyzed and current and future strategies for potential circumvention of severe immune responses toward alginate-based devices are reviewed and suggested.